title: Association of smoking behavior with an odorant receptor allele telomeric to the human major histocompatibility complex.
abstract: Smoking behavior has been associated in two independent European cohorts with the most common Caucasian human leukocyte antigen (HLA) haplotype (A1-B8-DR3). We aimed to test whether polymorphic members of the two odorant receptor (OR) clusters within the extended HLA complex might be responsible for the observed association, by genotyping a cohort of Hungarian women in which the mentioned association had been found. One hundred and eighty HLA haplotypes from Centre d'Etude du Polymorphisme Humain families were analyzed in silico to identify single-nucleotide polymorphisms (SNPs) within OR genes that are in linkage disequilibrium with the A1-B8-DR3 haplotype, as well as with two other haplotypes indirectly linked to smoking behavior. A nonsynonymous SNP within the OR12D3 gene (rs3749971(T)) was found to be linked to the A1-B8-DR3 haplotype. This polymorphism leads to a (97)Thr --> Ile exchange that affects a putative ligand binding region of the OR12D3 protein. Smoking was found to be associated in the Hungarian cohort with the rs3749971(T) allele (p = 1.05 x 10(-2)), with higher significance than with A1-B8-DR3 (p = 2.38 x 10(-2)). Our results link smoking to a distinct OR allele, and demonstrate that the rs3749971(T) polymorphism is associated with the HLA haplotype-dependent differential recognition of cigarette smoke components, at least among Caucasian women.
authors.affiliation: Institut für Immungenetik, Charité-Universitätsmedizin Berlin , Berlin, Germany.
authors.forename: Pablo Sandro Carvalho
authors.initials: PS
authors.lastname: Santos
authors.forename: George
authors.initials: G
authors.lastname: Füst
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Prohászka
authors.forename: Armin
authors.initials: A
authors.lastname: Volz
authors.forename: Roger
authors.initials: R
authors.lastname: Horton
authors.forename: Marcos
authors.initials: M
authors.lastname: Miretti
authors.forename: Chack-Yung
authors.initials: CY
authors.lastname: Yu
authors.forename: Stephan
authors.initials: S
authors.lastname: Beck
authors.forename: Barbara
authors.initials: B
authors.lastname: Uchanska-Ziegler
authors.forename: Andreas
authors.initials: A
authors.lastname: Ziegler
mesh_terms: D000483:Alleles; D015331:Cohort Studies; D005260:Female; D015788:HLA-A1 Antigen / Q000235:genetics; D015795:HLA-B8 Antigen / Q000235:genetics; D015803:HLA-DR3 Antigen / Q000235:genetics; D006239:Haplotypes; D006801:Humans; D006814:Hungary; D015810:Linkage Disequilibrium; D008285:Major Histocompatibility Complex; D020641:Polymorphism, Single Nucleotide; D018035:Receptors, Odorant / Q000235:genetics*; D012907:Smoking / Q000235:genetics*; D016615:Telomere / Q000235:genetics; D044465:White People / Q000235:genetics
chemical_list: D015788:HLA-A1 Antigen; D015795:HLA-B8 Antigen; D015803:HLA-DR3 Antigen; D018035:Receptors, Odorant